Physiological and psychological determinants of long-term diet-induced type 2 diabetes (T2DM) remission: A narrative review.

Type 2 diabetes mellitus (T2DM) is a highly prevalent metabolic disease, causing a heavy burden on healthcare systems worldwide, with related complications and anti-diabetes drug prescriptions. Recently, it was demonstrated that T2DM can be put into remission via significant weight loss using low-carbohydrate diets (LCDs) and very low-energy diets (VLEDs) in individuals with overweight and obesity. Clinical trials demonstrated remission rates of 25-77%, and metabolic improvements such as improved blood lipid profile and blood pressure were observed. In contrast, clinical trials showed that remission rate declines with time, concurrent with weight gain, or diminished weight loss. This review aims to discuss existing literature regarding underlying determinants of long-term remission of T2DM including metabolic adaptations to weight loss (e.g., role of gastrointestinal hormones), type of dietary intervention (i.e., LCDs or VLEDs), maintaining beta (ß)-cell function, early glycemic control, and psychosocial factors. This narrative review is significant because determining the factors that are associated with challenges in maintaining long-term remission may help in designing sustainable interventions for type 2 diabetes remission.

The effectiveness of erector spina plane, quadratus lumborum blocks, and intrathecal morphine for analgesia after cesarean: a randomized study.

OBJECTIVE: This prospective randomized study was conducted at Ataturk University Medical Faculty Hospital, Department of Anesthesia and Reanimation, from June 2022 to May 2023. The aim of this study was to compare the effectiveness of ultrasound-guided erector spinae plane block, quadratus lumborum block, and intrathecal morphine to decrease postoperative pain after cesarean section. METHODS: Sixty-term pregnant women who were scheduled for elective cesarean sections with spinal anesthesia were included. Patients were randomly divided into three groups (n=20 for each group): Group 1: Patients were administered intrathecal morphine during spinal anesthesia; Group 2: Patients performed bilateral erector spinae plane block postoperatively; and Group 3: Patients performed bilateral quadratus lumborum block postoperatively. In the postpartum care unit, patients received intravenous Patient-Controlled Analgesia. The Patient-Controlled Analgesia devices were set to administer an intravenous bolus of 25 µg fentanyl, with a lockout interval of 10 min. Opioid consumption and maximum pain score in the 24 postoperative hours were recorded. RESULTS: Patients in Group 1 had a longer time to first analgesic requirement compared to Group 2 (p=0.017). Opioid consumption and resting and moving visual analog score scores in the first 24 h postoperatively were similar between groups. CONCLUSION: All three methods, including intrathecal morphine, erector spinae plane block, and quadratus lumborum block, are efficacious and comparable in providing postoperative analgesia after cesarean under spinal anesthesia.

Posttraumatic epilepsy in critically ill children with traumatic brain injury.

PURPOSE: The aim of this study was to determine the clinical, laboratory, and radiological factors related with posttraumatic epilepsy (PTE). METHODS: The study is a multicenter descriptive cross-sectional cohort study. Children who followed up for TBI in the pediatric intensive care unit between 2014 and 2021 were included. Demographic data and clinical and radiological parameters were recorded from electronic case forms. All patients who were in the 6-month posttraumatic period were evaluated by a neurologist for PTE. RESULTS: Four hundred seventy-seven patients were included. The median age at the time of trauma was 66 (IQR 27-122) months, and 298 (62.5%) were male. Two hundred eighty (58.7%) patients had multiple traumas. The mortality rate was 11.7%. The mean duration of hospitalization, pediatric intensive care unit hospitalization and mechanical ventilation, Rotterdam score, PRISM III score, and GCS at admission were higher in patients with epilepsy (p < 0.05). The rate of epilepsy was higher in patients with severe TBI, cerebral edema on tomography and clinical findings of increased intracranial pressure, blood transfusion in the intensive care unit, multiple intracranial hemorrhages, and intubated patients (p < 0.05). In logistic regression analysis, the presence of intracranial hemorrhage in more than one compartment of the brain (OR 6.13, 95%CI 3.05-12.33) and the presence of seizures (OR 9.75, 95%CI 4.80-19.83) were independently significant in terms of the development of epilepsy (p < 0.001). CONCLUSIONS: In this multicenter cross-sectional study, intracranial hemorrhages in more than one compartment and clinical seizures during intensive care unit admission were found to be independent risk factors for PTE development in pediatric intensive care unit patients with TBI.

Clinical and Genetic Spectrum of Myotonia Congenita in Turkish Children.

BACKGROUND: Myotonia congenita is the most common form of nondystrophic myotonia and is caused by Mendelian inherited mutations in the CLCN1 gene encoding the voltage-gated chloride channel of skeletal muscle. OBJECTIVE: The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort. METHODS: Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in different geographical regions of Türkiye were retrospectively investigated. RESULTS: Fifty-four patients (mean age:15.2 years (±5.5), 76% males, with 85% Becker, 15% Thomsen form) from 40 families were included. Consanguineous marriage rate was 67%. 70.5% of patients had a family member with Myotonia congenita. The mean age of disease onset was 5.7 (±4.9) years. Overall 23 different mutations (2/23 were novel) were detected in 52 patients, and large exon deletions were identified in two siblings. Thomsen and Becker forms were observed concomitantly in one family. Carbamazepine (46.3%), mexiletine (27.8%), phenytoin (9.3%) were preferred for treatment. CONCLUSIONS: The clinical and genetic heterogeneity, as well as the limited response to current treatment options, constitutes an ongoing challenge. In our cohort, recessive Myotonia congenita was more frequent and novel mutations will contribute to the literature.

Serum endocan levels in patients with habitual abortion.

AIM: The aim of this study was to investigate whether there is a new factor in the etiology of recurrent loss of pregnancy. For this purpose, serum malondialdehyde (MDA) and nitric oxide (NO) levels as indicators of oxidative stress, and endocan levels, a marker of vascular dysfunction, were investigated in patients diagnosed with habitual abortion. MATERIALS AND METHODS: The research was conducted as a prospective case-control study. Patients aged 18-40 years with two or more consecutive pregnancy losses revealed by ultrasonographic or histopathological examination, and with no pathology capable of causing habitual abortion were included in the study group. Patients with no history of abortion, with at least one healthy pregnancy, who were planning pregnancies, and who presented to the outpatient clinic for routine prepregnancy tests were selected as the control group. Two groups were established-habitual abortion (n = 30) and control (n = 29). At the end of the menstrual cycle, blood samples were collected and centrifuged. Serum NO, MDA, and endocan levels were studied. RESULTS: Serum endocan, NO, and MDA levels were higher in women with habitual abortion compared to healthy controls. Pearson's correlation analysis revealed a positive correlation between serum endocan levels and NO and MDA levels. A positive correlation was also observed between serum MDA and NO levels. Multiple regression was run to predict serum endocan levels from MDA and NO levels. These variables emerged as statistically significant predictors of endocan. CONCLUSION: These findings suggest the presence of vascular endothelial dysfunction in patients with habitual abortion.

Pediatric-Onset Chronic Inflammatory Demyelinating Polyneuropathy: A Multicenter Study.

BACKGROUND: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. METHODS: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. RESULTS: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 44.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). CONCLUSIONS: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.

Aspects of autism spectrum disorder and correlation with neuroimaging findings in tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) patients may have different specific neuropsychological deficits related to the location of the tubers. Autism spectrum disorders (ASD) are common in TSC patients but the relationship between these diagnoses has not been formally explored. In this study we sought to examine brain Magnetic Resonance Imaging (MRI) findings in TSC patients with ASD. METHODS: We evaluated 34 TSC patients on the basis of DSM-V diagnostic criteria for ASD, Wechsler Intelligence Scale for Children (WISC-R), psychiatrist's examination and also structured parent interviews. The number and localization of the tubers, postcontrast signal characteristics of the tubers, SWI findings, DWI findings on brain MRI were recorded. Demographic features, epilepsy histories, number of antiseizure medications, cognitive status were eveluated also. Patients were divided into two groups: ASD group, which represented group 1 and group 2 consisting of patients without any ASD symptoms. RESULTS: In our study, the mean number of tuber count was 21.8 in patients with ASD patients (Group 1, n = 13) and 12.4 in other TSC patients without ASD (Group 2, n = 21). Rate of tubers in prefrontal cortex/whole tubers (0.51) in patients with ASD was determined to be higher in group 1 (p = 0.003). Also a significant difference was detected between generalize epileptiform activities on EEG and the rate of DRE (p = 0.002; p = 0.001) between groups. Cognitive disturbances and infantile spasm history were similar between groups. TSC2 mutations have been identified in 29 (86%) patients. CONCLUSION: The mean of total tuber count and the rate of the location in the prefrontal cortex were determined to be higher in TSC patients with ASD. Specific areas on brain MRI may help understanding the development of ASD in TSC patients.

The effectiveness of erector spina plane, quadratus lumborum blocks, and intrathecal morphine for analgesia after cesarean: a randomized study

SUMMARY OBJECTIVE: This prospective randomized study was conducted at Ataturk University Medical Faculty Hospital, Department of Anesthesia and Reanimation, from June 2022 to May 2023. The aim of this study was to compare the effectiveness of ultrasound-guided erector spinae plane block, quadratus lumborum block, and intrathecal morphine to decrease postoperative pain after cesarean section. METHODS: Sixty-term pregnant women who were scheduled for elective cesarean sections with spinal anesthesia were included. Patients were randomly divided into three groups (n=20 for each group): Group 1: Patients were administered intrathecal morphine during spinal anesthesia; Group 2: Patients performed bilateral erector spinae plane block postoperatively; and Group 3: Patients performed bilateral quadratus lumborum block postoperatively. In the postpartum care unit, patients received intravenous Patient-Controlled Analgesia. The Patient-Controlled Analgesia devices were set to administer an intravenous bolus of 25 μg fentanyl, with a lockout interval of 10 min. Opioid consumption and maximum pain score in the 24 postoperative hours were recorded. RESULTS: Patients in Group 1 had a longer time to first analgesic requirement compared to Group 2 (p=0.017). Opioid consumption and resting and moving visual analog score scores in the first 24 h postoperatively were similar between groups. CONCLUSION: All three methods, including intrathecal morphine, erector spinae plane block, and quadratus lumborum block, are efficacious and comparable in providing postoperative analgesia after cesarean under spinal anesthesia.

A Case with NAD(P)HX Dehydratase (NAXD) Deficiency: A Newly Defined Mutation in a Novel Neurodegenerative Disorder.

Introduction: Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are required redox equivalents for essential biochemical reactions. Their hydrated forms, NADHX and NAD(P)HX, are inhibitors for several dehydrogenases and cause harmful byproducts. NAD(P)HX dehydratase (NAXD) and NAD(P)HX epimerase (NAXE) together form the nicotinamide repair system. Case Presentation: A 7-month-old boy was admitted due to myoclonic seizures, impaired consciousness, and rapid loss of head control. One of his siblings regressed after a febrile seizure and died at 7 months. He had lethargy and axial hypotonia but skin lesions and organomegaly were not noted. Basal metabolic tests were within normal limits except serum and cerebrospinal fluid lactate levels, which were mildly elevated. Mitochondrial cocktail was added to the antiepileptic treatment with suspicion of mitochondrial disease. Whole-exome sequencing showed a novel homozygous mutation (c.247G>A) in the NAXD gene. His seizures stopped within a few weeks. However, he died at the age of 18 months. Discussion: Prominent features of NAXD deficiency are progressive neurological deterioration after fever, cardiomyopathy, skin lesions, and premature death. Unlike the cases reported in the literature, our patient had neither preceding fever nor skin lesion during follow-up. It appears that cases show phenotypic diversity.

How did the COVID-19 Pandemic Affect Pediatric Neurologists?

BACKGROUND: In addition to physical health, pandemics affect mental health. The aim was to reveal problems encountered during the coronavirus disease 2019 (COVID-19) pandemic by pediatric neurologists and pediatric neurology residents in Turkey. METHODS: Participants were sent a survey form using Google Forms between November 05, 2020, and December 07, 2020. The form included questions about demographic information, changes to services offered, effects of the COVID-19 pandemic on patient follow-up/treatment and doctor decision-making, the Depression-Anxiety-Stress Scale 21, and the Impact of Events scale for posttraumatic stress disorder. RESULTS: A total of 232 pediatric neurologists and residents (mean age: 40.67 ± 7.8 years) participated. Of these 182 participants (78.4%) stated the pandemic had affected decisions during diagnosis and treatment management. A total of 222 participants completed the Depression-Anxiety-Stress Scale 21 and Impact of Events scale. Of these, points at levels that were "severe and very severe" were present for 42 participants (18.9%) for depression, 29 participants for anxiety (13%), and 31 participants for stress (14%). Impact of Events scale points were high at "severe" levels for 122 participants (55%). All scores were higher for those with individuals at risk in terms of COVID-19 in their family compared with those without individuals at risk in the family (P < 0.05). CONCLUSIONS: As we emerge from the destruction caused by COVID-19, it will be beneficial not only for our professional practice but also in terms of our individual health to learn lessons that will assist in managing the next pandemic waiting in our future.

KMT2B-Related Dystonia: Challenges in Diagnosis and Treatment.

In this study, we report the first known Turkish case of a novel nonsense mutation c.2453dupT (p.M818fs*28) in the KMT2B (NM_014727.2) gene diagnosed in a male patient with KMT2B-related dystonia (DYT-KMT2B, DYT-28, Dystonia*-28), which is a complex, childhood-onset, progressive, hereditary dystonia. The patient, who is followed up from 9 to 13 years of age, had dysmorphic features, developmental delay, short stature, and microcephaly, in addition to focal dystonia and hemichorea (in the right and left lower extremities). Generalized dystonia involving bulbar and cervical muscles, in addition to dystonic cramps, myoclonus, and hemiballismus, were also observed during the course of the follow-up. While he was able to perform basic functions like eating, climbing stairs, walking, and writing with the aid of levodopa and trihexyphenidyl treatment, his clinical status gradually deteriorated secondary to progressive generalized dystonia in the 4-year follow-up. Deep brain stimulation has been shown to be effective in several patients which could be the next preferred treatment for the patient.

The effect of coronavirus disease 2019 on anxiety levels of children with cystic fibrosis and healthy peers.

BACKGROUND: Cystic fibrosis (CF) is a chronic disease causing recurrent respiratory tract infections. Viral respiratory tract infections are more severe in CF. The first case of coronavirus disease 2019 (COVID-19) was seen in Turkey on March 11, 2020, and nationwide school closure and lockdown were implemented. School closure and home confinement might have adverse effects on children's physical and mental health. In this study, we aimed to compare the effect of the COVID-19 pandemic on psychological reactions of CF patients and healthy controls. METHODS: This is a controlled cross-sectional study including 7-18-year-old children with CF. The survey included questions regarding family environment and peer relations, self-care, and psychological reactions to the COVID-19 pandemic. The questionnaire was administered to children via telephone calls under parental supervision. RESULTS: We evaluated 132 CF patients and 135 of their healthy peers. Mean age was 11.5 ± 2.9 years in the CF group and 11.8 ± 3.2 years in the control group (P = 0.98). There were 55 girls (41.7%) in the CF group and 81 girls (60%) in the control group (P = 0.027). The socioeconomic status of their families was similar. The CF patients were found to be less anxious for family members at risk of COVID-19, less upset about school closure, and less anxious about the COVID-19 pandemic (P < 0.001, 0.02, 0.01, respectively). CONCLUSIONS: Cystic fibrosis patients seem to show more resilience in coping with the pandemic. Appropriate psychological support should be provided to them and resilience strategies in coping with the pandemic should be nurtured.

Granisetron or ondansentron to prevent hypotension after spinal anesthesia for elective cesarean delivery: A randomized placebo-controlled trial.

STUDY OBJECTIVE: This study aimed to compare the effects of high doses of ondansetron and granisetron before spinal anesthesia on hemodynamic parameters in patients undergoing elective cesarean section. DESIGN: A double-blinded randomized placebo-controlled trial. SETTING: Operating room. PATIENTS: A total of 120 parturients with term pregnancy undergoing elective cesarean section with combined spinal-epidural anesthesia were included. INTERVENTIONS: Three groups (n = 40 for each group) were formed by randomization. Five minutes before the anesthesia procedure, Group I received 8 mg intravenous (IV) ondansetron diluted in 10 ml normal saline, Group II received IV 3 mg granisetron diluted in 10 ml normal saline, and Group III received IV 10 ml normal saline. MEASUREMENTS: Following intrathecal drug administration, intraoperative hemodynamic changes were recorded every 2 min for 20 min and then every 5 min until the end of the operation. MAIN RESULTS: Twenty patients (50%) in Group I, 12 patients (30%) in Group II, and 29 patients (72.5%) in Group III had hypotension requiring treatment with IV ephedrine (P = 0.001). The ephedrine requirement in Group III was significantly higher than in Groups I (P = 0.033) and II (P < 0.001). Also, the ephedrine requirement in Group II was lower than in Group I, but the difference was not statistically significant (P = 0.055). The mean arterial pressure for the three groups differed in the 10th, 18th, and 60th minutes. The number of patients with nausea or vomiting was lower in Groups I and II than in Group III (P < 0.001). At 5 min, the Apgar scores were higher than 8 for all neonates. Postoperative scores for the visual analogue scale were similar for all groups. CONCLUSIONS: It was concluded that prophylactic IV administration of 3 mg of granisetron or 8 mg of ondansetron before spinal anesthesia results in a significantly lower ephedrine requirement compared to placebo.

Combined spinal epidural anesthesia in obese parturients undergoing cesarean surgery : A single-blinded randomized comparison of lateral decubitus and sitting positions.

BACKGROUND: There is a significant increase in number of obese pregnant women worldwide. Obese parturients undergoing cesarean section have a higher risk for hypotension and require higher doses of vasopressors following spinal anesthesia compared to nonobese parturients. OBJECTIVE: This study aimed to compare the maternal hemodynamic changes when combined spinal-epidural anesthesia (CSEA) is induced in the left lateral decubitus and sitting positions in obese pregnant women undergoing elective cesarean section. MATERIAL AND METHODS: In this study, pregnant women with full-term gestation diagnosed as obese undergoing elective cesarean section were included. Two groups were formed: the CSEA was performed in left lateral position in group I (n = 50) and in sitting position in group II (n = 50). At the end of the CSEA procedure, patients were placed in the supine position. When the sensory block reached at the upper level of T6 dermatome, surgery was initiated. Hemodynamic, anesthetic and neonatal parameters were recorded. RESULTS: In all patients, CSEA was successful and sufficient anesthesia was provided for surgery. Time to reach T6 dermatome sensory level in group II was found to be longer than group I (P = 0.011). At 20 min after spinal injection, the maximum sensory block level was similar in both groups. There were no significant differences between groups in terms of sensory block time and the time to requiring postoperative supplemental analgesics. There were no significant differences in terms of the volume of intravenous fluid administered, ephedrine and atropine requirements between groups. Both groups had similar systolic blood pressure, heart rate and oxygen saturation values during surgery and postoperatively. While both groups had similar diastolic blood pressure (DBP) values during surgery and at the 1st postoperative hour, group II had lower DBP values at the 2nd postoperative hour compared with group I (P = 0.04). CONCLUSION: Left lateral decubitus and sitting positions during performance of CSEA lead to similar maternal hemodynamic changes in obese pregnant women undergoing cesarean section.

Longitudinally extensive transverse myelitis in childhood: Clinical features, treatment approaches, and long-term neurological outcomes.

AIM: Longitudinally extensive transvers myelitis (LETM) is a rare and disabling condition in childhood. The aim of the present study was to share experiences from our center regarding the treatment features and clinical and radiologic course in our LETM patients in light of the literature data. MATERIAL AND METHOD: The study was designed as cross-sectional and included children who followed for LETM at our pediatric neurology clinic between 2010 and 2019. ATM was diagnosed according to the diagnostic criteria report from the Transverse Myelitis Consortium Working Group. LETM was defined as the presence of spinal cord lesions spanning a length of 3 or more consecutive vertebral segments. The patients' medical records were examined in terms of demographic characteristics, presenting symptoms, history of infection prior to and during LETM, prodromal history, neurological examination, laboratory and radiological findings, clinical course, and treatment. The Barthel Index was used to assess the physical independence in activities of daily living of patients with LETM who were followed for at least one year. RESULTS: A total of 15 (8 girl) patients were included in the study. The patients were between 1 and 17 years of age. Presenting symptoms included inability to walk in 12 patients, incontinence in 9 patients, low back pain in 4 patients, abdominal pain in 2 patients, and inability to use the arms in 2 patients. In Barthel Index assessment of physical independence in activities of daily living, 8 patients were evaluated as completely independent, 3 patients as moderately dependent, and 2 patients as slightly dependent. When the 4 patients with motor area impairment and moderate dependency according to the Barthel Index were examined, it was noted that all of them had been admitted 4 days after the onset of symptoms and that 2 (13.3%) had cervicothoracic involvement and 2 (13.3%) had involvement of the entire cord. CONCLUSION: Shorter delay from symptom onset to initiation of immunomodulatory therapy as well as effective rehabilitation resulted in favorable outcomes, with the most noticeable improvement in the areas of motor function and incontinence.

Retrospective evaluation of patients with X-linked adrenoleukodystrophy with a wide range of clinical presentations: a single center experience.

OBJECTIVES: X-linked adrenoleukodystrophy (X-ALD), is a peroxisomal inborn error of metabolism caused due to the loss of function variants of ABCD1 gene that leads to accumulation of very long chain fatty acids (VLCFAs) in several tissues including the neurological system. Childhood cerebral X-ALD (CCALD) is the most common and severe form of X-ALD, if left untreated. Allogenic hematopoietic stem cell transplantation (HSCT) is the only available therapy that halts neurological deterioration in CCALD. We present 12 patients with several subtypes of X-ALD that were followed-up in a single center. METHODS: Data of 12 patients diagnosed with X-ALD were documented retrospectively. Demographics, age of onset, initial symptoms, endocrine and neurological findings, VLCFA levels, neuroimaging data, molecular genetic analysis of ABCD1 gene, and disease progress were documented. RESULTS: Mean age of initiation of symptoms was 7.9 years and mean age of diagnosis was 10.45 years. Eight patients had the CCALD subtype, while two had the cerebral form of AMN, one had the adult form of cerebral ALD, and one patient had the Addison only phenotype. The most common initial symptoms involved the neurological system. Loes scores varied between 0 and 12. Seven patients with CCALD underwent HSCT, among them three patients died. The overall mortality rate was 25%. CONCLUSIONS: Patients with X-ALD should be carefully followed up for cerebral findings and progression, since there is no genotype-phenotype correlation, and the clinical course cannot be predicted by family history. HSCT is the only available treatment option for patients with neurological deterioration.

Risk of recurrence after antiepileptic withdrawal: Was it a good decision or not?

Background: The aim of this study was to identify the demographic-clinical variables affecting idiopathic epilepsy (IE) [called genetic generalized epilepsy (GGE)] recurrence and determine cut-off values that can be used in pediatric neurology practice for children with IE/GGE. Methods: A total of 250 children and adolescents with IE/GGE were included and retrospectively evaluated. The patients' hospital records were examined in order to identify possible electro-clinical features affecting epilepsy recurrence. Results: The overall rate of recurrence in the patients was 46%; the age at onset of seizures in recurrence group was lower (P = 0.040) and the age at last seizure was higher in the recurrence group (P < 0.001) than that in the non-recurrence group. Other factors found to be related to recurrence were the shorter duration of the seizure-free period (P = 0.030), shorter interval between the last seizure and antiepileptic drug (AED) withdrawal (P = 0.003), shorter duration of AED withdrawal (P = 0.005), and the existence of abnormalities on sleep electroencephalogram (EEG) during AED withdrawal (P = 0.010) and at the 6th month of withdrawal (P < 0.001). According to receiver operating characteristic (ROC) analysis, the risk of IE recurrence was higher in children who were younger than 3.6 years old (sensitivity: 65.6%, specificity: 62.7%), children with a seizure-free period that was shorter than 35.5 months (sensitivity: 89.6%, specificity: 32.8%), and children whose drug withdrawal period was shorter than 4.5 months (sensitivity: 56.3%, specificity: 71.6%). Conclusion: This study defined some electro-clinical factors that could guide clinicians when deciding to withdraw AEDs with regard to recurrence risk after evaluating a homogenous population of children with a diagnosis of IE/GGE.

The effect of copper intrauterine device use duration on uterine and ovarian blood flow parameters: A prospective cross-sectional study.

PURPOSE: This prospective cross-sectional study aimed to compare uterine and ovarian arterial Doppler signals in regularly menstruating patients who had been using copper intrauterine devices (IUD) for different durations. METHODS: Four groups of participants were formed (n = 30 for each) depending on the duration of copper IUD use: less than 1 year (group 1), 1 to 3 years (group 2), and over 3 years (group 3). Women without IUDs formed the control group. All participants were called in on the fifth-eighth days of their menstrual cycle for Doppler blood flow assessment. The pulsatility index (PI) and resistance index (RI) values were recorded in uterine and ovarian arteries. RESULTS: The groups 2 and 3 had significantly higher uterine artery PI and RI values than groups 1 and 4. Furthermore, group 2 had uterine and ovarian artery PI and RI values similar to those of group 3. There was a positive relationship between uterine and ovarian arteries' PI and RI values with the duration of IUD use. CONCLUSIONS: The presence of an IUD for over a year seems to cause changes in the uterine artery PI and RI values assessed by Doppler ultrasonography.

Pediatric headache: Are the red flags misleading or prognostic?

BACKGROUND: Symptoms and findings called orange or red flags may indicate the etiology of pediatric headaches and may point to a life-threatening situation requiring urgent treatment and thus can alter patient management. These findings can be either misleading or prognostic for clinicians. We aimed to identify the etiology and prognostic value of orange/red flags in pediatric patients. METHODS: This study included 810 children with headaches who underwent neuroimaging due to the existence of orange/red flags. Their hospital records were examined to obtain demographical, clinical, laboratory data, and re-classify the headaches and determine orange/red flags on admission. RESULTS: Secondary causes were identified in 17.0% (n: 138) of patients, however, those who were diagnosed with a life-threatening headache that required emergency treatment were 5.2% of all patients and 30.4% of the patients diagnosed with a secondary headache. Those with secondary headaches and with life threatening secondary headaches which required urgent treatment were younger (p = 0,018, p = 0,022), had more emergency department visits (p < 0,001), and acute onsets (p < 0,001). Red flags, like systemic symptoms (p < 0,001), sudden onset (p = 0,023, p = 0.039), papilledema (p < 0,001), and progressive headaches (p = 0,048, p = 0.006), were more common with secondary headaches and its subgroup, while headache awakening from sleep (p = 0.009) and family history of primary headache (P > 0,001) were more common in primary headaches. No correlation existed between the number of red flags and etiology. However, older age (p = 0,001) and a shorter duration between symptoms and admission (p = 0,032), and the number of emergency service visits (p = 0,020) increased with increasing red flags. CONCLUSIONS: Physicians always look for flags when they encounter patients with headaches, which is a common symptom, so as not to overlook anything. However, red flags do not always mean that the underlying cause requires emergency treatment and the severity of the cause is not correlated with the number of flags.

Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia.

Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 ± 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 ± 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 ± 5.1 years, SD) and later tetraplegia (mean age: 16.1 ± 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 ± 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 ± 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.